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Organic Chemistry
Table of Contents
Unit 19 Overview: Aldehydes & Ketones: Nucleophilic Addition
19.1 Naming Aldehydes and Ketones
19.2 Preparing Aldehydes and Ketones
19.3 Oxidation of Aldehydes and Ketones
19.4 Nucleophilic Addition Reactions of Aldehydes and Ketones
19.5 Nucleophilic Addition of H2O: Hydration
19.6 Nucleophilic Addition of HCN: Cyanohydrin Formation
19.7 Nucleophilic Addition of Hydride and Grignard Reagents: Alcohol Formation
19.8 Nucleophilic Addition of Amines: Imine and Enamine Formation
19.9 Nucleophilic Addition of Hydrazine: The Wolff–Kishner Reaction
19.10 Nucleophilic Addition of Alcohols: Acetal Formation
19.11 Nucleophilic Addition of Phosphorus Ylides: The Wittig Reaction
19.12 Biological Reductions
19.13 Conjugate Nucleophilic Addition to α,β‑Unsaturated Aldehydes and Ketones
19.14 Spectroscopy of Aldehydes and Ketones

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19.9 Nucleophilic Addition of Hydrazine: The Wolff–Kishner Reaction

Citation:

The Wolff-Kishner reaction is a powerful tool for converting aldehydes and ketones to alkanes. It's a two-step process involving hydrazone formation and nitrogen gas elimination, offering a unique approach to carbonyl reduction.

Compared to catalytic hydrogenation, Wolff-Kishner shines when selectivity is key. It's gentler on sensitive substrates and doesn't affect other functional groups like alkenes or alkynes, making it a versatile choice in organic synthesis.

Wolff-Kishner Reaction

Wolff-Kishner reaction mechanism

  • Two-step process converting aldehydes and ketones to alkanes
  • Step 1: Hydrazone formation
    • Carbonyl compound reacts with hydrazine ($N_2H_4$) under basic conditions (sodium or potassium hydroxide as base)
    • Hydrazine acts as nucleophile attacking electrophilic carbonyl carbon
    • Tetrahedral intermediate eliminates water forming carbon-nitrogen double bond creating hydrazone
  • Step 2: Nitrogen gas elimination
    • Upon heating to 200°C or higher hydrazone undergoes decomposition
    • Carbon-nitrogen double bond reduced to single bond with simultaneous elimination of nitrogen gas ($N_2$)
    • Resulting carbanion intermediate abstracts proton from solvent or base forming final alkane product

Conversion of carbonyls to alkanes

  • Wolff-Kishner reaction reduces carbonyl group of aldehydes and ketones to methylene group ($CH_2$)
  • Proceeds through formation of hydrazone intermediate by nucleophilic addition of hydrazine to carbonyl group
  • Upon heating hydrazone decomposes eliminating nitrogen gas and forming carbanion intermediate
  • Carbanion abstracts proton from solvent or base resulting in formation of corresponding alkane
  • Overall result is replacement of carbonyl group with methylene group reducing oxidation state of carbon by two

Wolff-Kishner vs catalytic hydrogenation

  • Both Wolff-Kishner reduction and catalytic hydrogenation convert aldehydes and ketones to alkanes
  • Catalytic hydrogenation
    1. Involves direct addition of hydrogen gas ($H_2$) to carbonyl group using metal catalyst (palladium, platinum, or nickel)
    2. Performed under high pressure and often at elevated temperatures
    3. Catalyst facilitates dissociation of hydrogen gas and transfer of hydrogen atoms to carbonyl carbon and oxygen
  • Wolff-Kishner reduction
    1. Involves formation of hydrazone intermediate using hydrazine followed by decomposition and nitrogen gas elimination
    2. Performed under basic conditions and requires high temperatures (200°C or higher)
    3. Hydrazone acts as masked form of carbonyl group allowing for reduction to occur through different mechanism
  • Advantages and disadvantages
    • Catalytic hydrogenation generally faster and can be performed under milder conditions compared to Wolff-Kishner reduction
    • Wolff-Kishner reduction advantageous when substrate sensitive to hydrogenation conditions or when catalyst may be poisoned by other functional groups present in molecule
    • Wolff-Kishner reduction often used when selectivity required as it does not reduce other functional groups (alkenes or alkynes) which may be reduced under catalytic hydrogenation conditions

Reaction Conditions and Considerations

  • Solvent choice: Typically, high-boiling solvents like ethylene glycol or diethylene glycol are used due to the high temperatures required
  • Base: Strong bases such as potassium hydroxide or sodium hydroxide are essential for the reaction
  • Reduction: The Wolff-Kishner reaction is a reduction process, lowering the oxidation state of the carbonyl carbon
  • Elimination reaction: The final step involves an elimination reaction, where nitrogen gas is expelled
  • Temperature: High temperatures (200°C or higher) are necessary to drive the elimination of nitrogen and complete the reduction

Key Terms to Review (23)

β Diketone: A β-diketone is an organic compound containing two ketone groups separated by a carbon atom, which is the beta (β) position relative to each ketone group. These molecules are characterized by the presence of hydrogen atoms on the carbon between the two carbonyl (C=O) groups, making them acidic and prone to enolate ion formation.
Wolff–Kishner reaction: The Wolff–Kishner reaction is a chemical process used to convert carbonyl groups in aldehydes and ketones into methylene (-CH2-) groups by treating them with hydrazine (N2H4) and a strong base. It effectively removes the oxygen atom from the carbonyl group, resulting in a saturated hydrocarbon.
Alkane: Alkanes are a class of saturated hydrocarbons composed entirely of single-bonded carbon and hydrogen atoms. They are the simplest organic compounds and form the basis for many other organic molecules and reactions.
Electrophilic: Electrophilic refers to a species or reagent that is attracted to or seeks out electron-rich regions, typically in organic chemistry reactions. These species are often positively charged or have a partial positive charge, and they interact with and form bonds with nucleophiles, which are electron-rich species.
Base: A base is a substance that can accept a proton (H+) from an acid, forming a conjugate acid-base pair. Bases are characterized by their ability to increase the pH of a solution, neutralize acids, and serve as nucleophiles in various chemical reactions.
Aldehyde: An aldehyde is a class of organic compounds containing a carbonyl group (C=O) where the carbon atom is bonded to one hydrogen atom and one alkyl or aryl group. Aldehydes are important functional groups in organic chemistry and are involved in various reactions and synthesis pathways.
Ketone: A ketone is a functional group in organic chemistry that consists of a carbonyl group (a carbon-oxygen double bond) bonded to two alkyl or aryl groups. Ketones are widely encountered in various organic chemistry topics, including the hydration of alkynes, oxidative cleavage of alkynes, organic synthesis, oxidation and reduction reactions, and the chemistry of aldehydes and ketones.
Nucleophile: A nucleophile is a species that donates a pair of electrons to form a covalent bond with another atom or molecule. Nucleophiles are central to understanding many organic reactions, including polar reactions, electrophilic addition reactions, and nucleophilic substitution reactions.
Palladium: Palladium is a rare and valuable transition metal that has unique catalytic properties, making it an important element in various organic chemistry reactions. It is commonly used as a catalyst to facilitate chemical transformations and is particularly relevant in the context of biological reactions, the reduction of alkenes, oxidation and reduction processes, and the Wolff-Kishner reaction.
Platinum: Platinum is a rare, dense, and highly valuable precious metal that is widely used in various scientific and industrial applications. It is known for its exceptional catalytic properties, corrosion resistance, and high melting point, making it a crucial element in organic chemistry and related fields.
Oxidation State: Oxidation state is a measure of the degree of oxidation of an atom in a chemical compound. It is the hypothetical charge that an atom would have if all bonds to atoms of different elements were completely ionic, with the more electronegative atom(s) assigned the full negative charge(s).
Elimination Reaction: An elimination reaction is a type of organic reaction in which two atoms or groups are removed from a molecule, typically resulting in the formation of a carbon-carbon double bond or a carbon-carbon triple bond. This process is an important step in the synthesis of alkenes and alkynes, as well as in various other organic transformations.
Reduction: Reduction is a chemical process that involves the gain of electrons by a molecule or atom, resulting in a decrease in its oxidation state. This term is particularly important in the context of various organic chemistry reactions and transformations.
Catalytic Hydrogenation: Catalytic hydrogenation is a chemical process where hydrogen gas is used to reduce unsaturated organic compounds, such as alkenes, aromatic rings, and carbonyl groups, in the presence of a metal catalyst. This reaction allows for the selective and controlled addition of hydrogen to these functional groups, leading to the formation of new, more saturated compounds.
Carbonyl Compound: A carbonyl compound is a class of organic compounds that contain a carbonyl group, which is a carbon atom double-bonded to an oxygen atom. These compounds are fundamental in organic chemistry and play a crucial role in various reactions and transformations, including the topics of alcohols from carbonyl compounds, the Wolff-Kishner reduction, nucleophilic acyl substitution, enolate ion formation, alkylation of enolate ions, and intramolecular aldol reactions.
Tetrahedral Intermediate: A tetrahedral intermediate is a key reaction step that occurs in many organic chemistry reactions, where a trigonal planar carbonyl carbon temporarily becomes a tetrahedral carbon with four bonded atoms. This transient intermediate is crucial for understanding the mechanisms of various nucleophilic addition and substitution reactions.
Hydrazone: A hydrazone is a functional group formed by the condensation reaction between a carbonyl compound (such as an aldehyde or ketone) and a hydrazine. This reaction results in the formation of a carbon-nitrogen double bond with a nitrogen atom attached to another nitrogen atom.
Methylene Group: The methylene group, denoted as -CH2-, is a fundamental structural unit in organic chemistry. It consists of a carbon atom bonded to two hydrogen atoms and is an important functional group in many organic compounds. The methylene group is a key component in various reactions and plays a crucial role in the context of the Wolff–Kishner Reduction, a nucleophilic addition reaction involving hydrazine.
Hydrazine: Hydrazine is a colorless, flammable liquid with a distinctive ammonia-like odor. It is a highly reactive and reducing compound that finds applications in various chemical reactions and processes, particularly in the context of nucleophilic addition reactions and the synthesis of amines.
Nickel: Nickel is a hard, silvery-white metal that is widely used in various industrial and commercial applications. It is known for its corrosion-resistant properties and its ability to catalyze chemical reactions. In the context of the Wolff–Kishner Reaction, nickel plays a crucial role as a catalyst in the reduction of hydrazones to alkanes.
Solvent: A solvent is a liquid substance that is capable of dissolving or dispersing one or more other substances, forming a solution. Solvents play a crucial role in chemical reactions, including the Wolff-Kishner reduction, by providing the medium in which the reactants interact and the products are formed.
Wolff-Kishner Reaction: The Wolff-Kishner reaction is a chemical transformation that reduces a carbonyl compound, such as an aldehyde or ketone, to an alkane by the use of hydrazine and a strong base. It is a valuable method for the deoxygenation of carbonyl groups, particularly in the context of organic synthesis.
Carbanion: A carbanion is a negatively charged species that contains a carbon atom with three bonds and a lone pair of electrons, giving it a formal negative charge. This species is crucial in various organic reactions, as it acts as a strong nucleophile and can participate in forming new bonds by attacking electrophiles.